{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,11]],"date-time":"2026-03-11T23:23:29Z","timestamp":1773271409141,"version":"3.50.1"},"reference-count":53,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,3,12]],"date-time":"2023-03-12T00:00:00Z","timestamp":1678579200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Western Norway Regional Health Authority","award":["912278"],"award-info":[{"award-number":["912278"]}]},{"name":"Western Norway Regional Health Authority","award":["91217"],"award-info":[{"award-number":["91217"]}]},{"name":"Western Norway Regional Health Authority","award":["F\u201312183\/4800003665"],"award-info":[{"award-number":["F\u201312183\/4800003665"]}]},{"name":"Western Norway Regional Health Authority","award":["F11635\u2013D11698"],"award-info":[{"award-number":["F11635\u2013D11698"]}]},{"name":"Western Norway Regional Health Authority","award":["501809"],"award-info":[{"award-number":["501809"]}]},{"name":"Western Norway Regional Health Authority","award":["423204"],"award-info":[{"award-number":["423204"]}]},{"DOI":"10.13039\/501100010738","name":"Stavanger University Hospital","doi-asserted-by":"publisher","award":["912278"],"award-info":[{"award-number":["912278"]}],"id":[{"id":"10.13039\/501100010738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010738","name":"Stavanger University Hospital","doi-asserted-by":"publisher","award":["91217"],"award-info":[{"award-number":["91217"]}],"id":[{"id":"10.13039\/501100010738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010738","name":"Stavanger University Hospital","doi-asserted-by":"publisher","award":["F\u201312183\/4800003665"],"award-info":[{"award-number":["F\u201312183\/4800003665"]}],"id":[{"id":"10.13039\/501100010738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010738","name":"Stavanger University Hospital","doi-asserted-by":"publisher","award":["F11635\u2013D11698"],"award-info":[{"award-number":["F11635\u2013D11698"]}],"id":[{"id":"10.13039\/501100010738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010738","name":"Stavanger University Hospital","doi-asserted-by":"publisher","award":["501809"],"award-info":[{"award-number":["501809"]}],"id":[{"id":"10.13039\/501100010738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010738","name":"Stavanger University Hospital","doi-asserted-by":"publisher","award":["423204"],"award-info":[{"award-number":["423204"]}],"id":[{"id":"10.13039\/501100010738","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Folke Hermansens Funding","award":["912278"],"award-info":[{"award-number":["912278"]}]},{"name":"Folke Hermansens Funding","award":["91217"],"award-info":[{"award-number":["91217"]}]},{"name":"Folke Hermansens Funding","award":["F\u201312183\/4800003665"],"award-info":[{"award-number":["F\u201312183\/4800003665"]}]},{"name":"Folke Hermansens Funding","award":["F11635\u2013D11698"],"award-info":[{"award-number":["F11635\u2013D11698"]}]},{"name":"Folke Hermansens Funding","award":["501809"],"award-info":[{"award-number":["501809"]}]},{"name":"Folke Hermansens Funding","award":["423204"],"award-info":[{"award-number":["423204"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>High-grade serous ovarian carcinoma (HGSOC) is the most common and deadliest ovarian cancer subtype. Despite advances in treatment, the overall prognosis remains poor. Regardless of efforts to develop biomarkers to predict surgical outcome and recurrence risk and resistance, reproducible indicators are scarce. Exploring the complex tumor heterogeneity, serum profiling of metabolites and lipoprotein subfractions that reflect both systemic and local biological processes were utilized. Furthermore, the overall impact on the patient from the tumor and the treatment was investigated. The aim was to characterize the systemic metabolic effects of primary treatment in patients with advanced HGSOC. In total 28 metabolites and 112 lipoproteins were analyzed by nuclear magnetic resonance (NMR) spectroscopy in longitudinal serum samples (n = 112) from patients with advanced HGSOC (n = 24) from the IMPACT trial with linear mixed effect models and repeated measures ANOVA simultaneous component analysis. The serum profiling revealed treatment-induced changes in both lipoprotein subfractions and circulating metabolites. The development of a more atherogenic lipid profile throughout the treatment, which was more evident in patients with short time to recurrence, indicates an enhanced systemic inflammation and increased risk of cardiovascular disease after treatment. The findings suggest that treatment-induced changes in the metabolome reflect mechanisms behind the diversity in disease-related outcomes.<\/jats:p>","DOI":"10.3390\/metabo13030417","type":"journal-article","created":{"date-parts":[[2023,3,13]],"date-time":"2023-03-13T04:04:00Z","timestamp":1678680240000},"page":"417","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Primary Treatment Effects for High-Grade Serous Ovarian Carcinoma Evaluated by Changes in Serum Metabolites and Lipoproteins"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8676-3046","authenticated-orcid":false,"given":"Cecilie","family":"Torkildsen","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Stavanger University Hospital, 4068 Stavanger, Norway"},{"name":"Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, 5020 Bergen, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7285-103X","authenticated-orcid":false,"given":"Marie","family":"Austdal","sequence":"additional","affiliation":[{"name":"Department of Research, Stavanger University Hospital, 4068 Stavanger, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7726-7684","authenticated-orcid":false,"given":"Ann-Charlotte","family":"Iversen","sequence":"additional","affiliation":[{"name":"Centre of Molecular Inflammation Research (CEMIR), Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway"},{"name":"Department of Gynecology and Obstetrics, St. Olavs Hospital, Trondheim University Hospital, 7006 Trondheim, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8582-6965","authenticated-orcid":false,"given":"Tone","family":"Bathen","sequence":"additional","affiliation":[{"name":"Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, 7491 Trondheim, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2157-8824","authenticated-orcid":false,"given":"Guro","family":"Giske\u00f8deg\u00e5rd","sequence":"additional","affiliation":[{"name":"K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Norwegian University of Science and Technology (NTNU), 7491 Trondheim, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabeth","family":"Nilsen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Stavanger University Hospital, 4068 Stavanger, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Grete","family":"Iversen","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Haukeland University Hospital, 5021 Bergen, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ragnar","family":"Sande","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Stavanger University Hospital, 4068 Stavanger, Norway"},{"name":"Department of Clinical Science, University of Bergen, 5020 Bergen, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0240-2770","authenticated-orcid":false,"given":"Line","family":"Bj\u00f8rge","sequence":"additional","affiliation":[{"name":"Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, 5020 Bergen, Norway"},{"name":"Department of Obstetrics and Gynecology, Haukeland University Hospital, 5021 Bergen, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6787-8518","authenticated-orcid":false,"given":"Liv","family":"Thomsen","sequence":"additional","affiliation":[{"name":"Centre for Cancer Biomarkers CCBIO, Department of Clinical Science, University of Bergen, 5020 Bergen, Norway"},{"name":"Department of Obstetrics and Gynecology, Haukeland University Hospital, 5021 Bergen, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.3322\/caac.21708","article-title":"Cancer statistics, 2022","volume":"72","author":"Siegel","year":"2022","journal-title":"CA Cancer J. Clin."},{"key":"ref_2","unstructured":"Cancer Registry of Norway (2021). Cancer in Norway 2021\u2014Cancer Incidence, Mortality, Survival and Prevalence in Norway, Cancer Registry of Norway."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2495","DOI":"10.1056\/NEJMoa1810858","article-title":"Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer","volume":"379","author":"Moore","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2484","DOI":"10.1056\/NEJMoa1103799","article-title":"A phase 3 trial of bevacizumab in ovarian cancer","volume":"365","author":"Perren","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1038\/bjc.2012.376","article-title":"Does tumour biology determine surgical success in the treatment of epithelial ovarian cancer? A systematic literature review","volume":"107","author":"Borley","year":"2012","journal-title":"Br. J. Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"497429","DOI":"10.1155\/2010\/497429","article-title":"Treatment for recurrent ovarian cancer\u2014at first relapse","volume":"2010","author":"Ushijima","year":"2010","journal-title":"J. Oncol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1038\/nature10166","article-title":"Integrated genomic analyses of ovarian carcinoma","volume":"474","year":"2011","journal-title":"Nature"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4335","DOI":"10.1158\/0008-5472.CAN-20-0521","article-title":"Multiomic Analysis of Subtype Evolution and Heterogeneity in High-Grade Serous Ovarian Carcinoma","volume":"80","author":"Geistlinger","year":"2020","journal-title":"Cancer Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1186\/s13048-022-01004-1","article-title":"Evolutionary perspectives, heterogeneity and ovarian cancer: A complicated tale from past to present","volume":"15","author":"Kubelac","year":"2022","journal-title":"J. Ovarian Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"280","DOI":"10.3322\/caac.21559","article-title":"Epithelial ovarian cancer: Evolution of management in the era of precision medicine","volume":"69","author":"Lheureux","year":"2019","journal-title":"CA Cancer J. Clin."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"eaaw5473","DOI":"10.1126\/science.aaw5473","article-title":"Metabolic reprogramming and cancer progression","volume":"368","author":"Faubert","year":"2020","journal-title":"Science"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1158\/2159-8290.CD-21-1059","article-title":"Hallmarks of Cancer: New Dimensions","volume":"12","author":"Hanahan","year":"2022","journal-title":"Cancer Discov."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e11487","DOI":"10.1016\/j.heliyon.2022.e11487","article-title":"Recent advances in understanding the metabolic plasticity of ovarian cancer: A systematic review","volume":"8","author":"Kobayashi","year":"2022","journal-title":"Heliyon"},{"key":"ref_14","first-page":"9950","article-title":"Metabolic reprogramming in epithelial ovarian cancer","volume":"13","author":"Nantasupha","year":"2021","journal-title":"Am. J. Transl. Res."},{"key":"ref_15","first-page":"2122","article-title":"Hypoxia promotes glycogen synthesis and accumulation in human ovarian clear cell carcinoma","volume":"40","author":"Iida","year":"2012","journal-title":"Int. J. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Yoon, H., and Lee, S. (2022). Fatty Acid Metabolism in Ovarian Cancer: Therapeutic Implications. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23042170"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e3927","DOI":"10.1002\/nbm.3927","article-title":"NMR-based metabolomics of biofluids in cancer","volume":"32","author":"Giskeodegard","year":"2018","journal-title":"NMR Biomed."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"333","DOI":"10.3322\/caac.21670","article-title":"Metabolomics in cancer research and emerging applications in clinical oncology","volume":"71","author":"Schmidt","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Saorin, A., Di Gregorio, E., Miolo, G., Steffan, A., and Corona, G. (2020). Emerging Role of Metabolomics in Ovarian Cancer Diagnosis. Metabolites, 10.","DOI":"10.3390\/metabo10100419"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3649","DOI":"10.1021\/acs.jproteome.9b00316","article-title":"Assessing Treatment Response and Prognosis by Serum and Tissue Metabolomics in Breast Cancer Patients","volume":"18","author":"Debik","year":"2019","journal-title":"J. Proteome Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"919522","DOI":"10.3389\/fonc.2022.919522","article-title":"Longitudinal Changes in Circulating Metabolites and Lipoproteins After Breast Cancer Treatment","volume":"12","author":"Giskeodegard","year":"2022","journal-title":"Front. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"23334","DOI":"10.1038\/srep23334","article-title":"Metabolic phenotyping for monitoring ovarian cancer patients","volume":"6","author":"Ke","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"642.e1","DOI":"10.1016\/j.ajog.2008.06.052","article-title":"Prospective validation of a laparoscopic predictive model for optimal cytoreduction in advanced ovarian carcinoma","volume":"199","author":"Fagotti","year":"2008","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.ygyno.2015.07.095","article-title":"Definition of a dynamic laparoscopic model for the prediction of incomplete cytoreduction in advanced epithelial ovarian cancer: Proof of a concept","volume":"139","author":"Petrillo","year":"2015","journal-title":"Gynecol. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1156","DOI":"10.1245\/ASO.2006.08.021","article-title":"A laparoscopy-based score to predict surgical outcome in patients with advanced ovarian carcinoma: A pilot study","volume":"13","author":"Fagotti","year":"2006","journal-title":"Ann. Surg. Oncol."},{"key":"ref_26","unstructured":"Helsedirektoratet (2022, December 27). Nasjonalt Handlingsprogram Med Retningslinjer for Diagnostikk, Behandling Og Oppf\u00f8lging Av gynekologisk Kreft (Norwegian). Available online: https:\/\/www.helsedirektoratet.no\/retningslinjer\/gynekologisk-kreft-handlingsprogram."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.ejca.2008.10.026","article-title":"New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1)","volume":"45","author":"Eisenhauer","year":"2009","journal-title":"Eur. J. Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/j.jmr.2009.11.012","article-title":"icoshift: A versatile tool for the rapid alignment of 1D NMR spectra","volume":"202","author":"Savorani","year":"2010","journal-title":"J. Magn. Reson."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1038\/s41416-022-01924-1","article-title":"Lipoprotein and metabolite associations to breast cancer risk in the HUNT2 study","volume":"127","author":"Debik","year":"2022","journal-title":"Br. J. Cancer"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"11962","DOI":"10.1021\/acs.analchem.8b02412","article-title":"Quantitative Lipoprotein Subclass and Low Molecular Weight Metabolite Analysis in Human Serum and Plasma by (1)H NMR Spectroscopy in a Multilaboratory Trial","volume":"90","author":"Jimenez","year":"2018","journal-title":"Anal. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1214\/aos\/1013699998","article-title":"The control of the false discovery rate in multiple testing under dependency","volume":"29","author":"Benjamini","year":"2001","journal-title":"Ann. Stat."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1274","DOI":"10.1016\/S1470-2045(17)30469-2","article-title":"Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1\/2 mutation (SOLO2\/ENGOT-Ov21): A double-blind, randomised, placebo-controlled, phase 3 trial","volume":"18","author":"Ledermann","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1","DOI":"10.18637\/jss.v067.i01","article-title":"Fitting Linear Mixed-Effects Models Using lme4","volume":"67","author":"Bates","year":"2015","journal-title":"J. Stat. Softw."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Madssen, T.S., Giskeodegard, G.F., Smilde, A.K., and Westerhuis, J.A. (2021). Repeated measures ASCA+ for analysis of longitudinal intervention studies with multivariate outcome data. PLoS Comput. Biol., 17.","DOI":"10.1371\/journal.pcbi.1009585"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"962431","DOI":"10.3389\/fmolb.2022.962431","article-title":"ALASCA: An R package for longitudinal and cross-sectional analysis of multivariate data by ASCA-based methods","volume":"9","author":"Jarmund","year":"2022","journal-title":"Front. Mol. Biosci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"97","DOI":"10.2174\/2213235X04666160613122429","article-title":"PCA as a practical indicator of OPLS-DA model reliability","volume":"4","author":"Worley","year":"2016","journal-title":"Curr. Metab."},{"key":"ref_37","unstructured":"R Core Team (2020). R: A Language and Environment for Statistical Computing, R Foundation for Statistical Computing."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1161\/01.CIR.82.2.495","article-title":"Atherogenic Lipoprotein Phenotype\u2014A Proposed Genetic-Marker for Coronary Heart-Disease Risk","volume":"82","author":"Austin","year":"1990","journal-title":"Circulation"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1057546","DOI":"10.3389\/fimmu.2022.1057546","article-title":"Cholesterol: An important actor on the cancer immune scene","volume":"13","author":"Halimi","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_40","first-page":"219","article-title":"The role of cholesterol metabolism in cancer","volume":"9","author":"Ding","year":"2019","journal-title":"Am. J. Cancer Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.it.2021.11.007","article-title":"The cholesterol pathway: Impact on immunity and cancer","volume":"43","author":"King","year":"2022","journal-title":"Trends Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1016\/j.immuni.2016.04.011","article-title":"A Cholesterol-Based Allostery Model of T Cell Receptor Phosphorylation","volume":"44","author":"Swamy","year":"2016","journal-title":"Immunity"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.3389\/fimmu.2020.01371","article-title":"Myeloid-Derived Suppressor Cells in Tumors: From Mechanisms to Antigen Specificity and Microenvironmental Regulation","volume":"11","author":"Yang","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Behbodikhah, J., Ahmed, S., Elyasi, A., Kasselman, L.J., De Leon, J., Glass, A.D., and Reiss, A.B. (2021). Apolipoprotein B and Cardiovascular Disease: Biomarker and Potential Therapeutic Target. Metabolites, 11.","DOI":"10.3390\/metabo11100690"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1038\/sj.bjc.6605264","article-title":"Serum triglyceride concentrations and cancer risk in a large cohort study in Austria","volume":"101","author":"Ulmer","year":"2009","journal-title":"Br. J. Cancer"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"274585","DOI":"10.1155\/2015\/274585","article-title":"Obesity and cancer progression: Is there a role of fatty acid metabolism?","volume":"2015","author":"Balaban","year":"2015","journal-title":"Biomed. Res. Int."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Lofterod, T., Mortensen, E.S., Nalwoga, H., Wilsgaard, T., Frydenberg, H., Risberg, T., Eggen, A.E., McTiernan, A., Aziz, S., and Wist, E.A. (2018). Impact of pre-diagnostic triglycerides and HDL-cholesterol on breast cancer recurrence and survival by breast cancer subtypes. BMC Cancer, 18.","DOI":"10.1186\/s12885-018-4568-2"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2349","DOI":"10.1158\/1055-9965.EPI-14-0458","article-title":"Serum lipid profile and risk of prostate cancer recurrence: Results from the SEARCH database","volume":"23","author":"Allott","year":"2014","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"712731","DOI":"10.3389\/fphys.2021.712731","article-title":"Dietary Polyphenol and Methylsulfonylmethane Supplementation Improves Immune, DAMP Signaling, and Inflammatory Responses During Recovery From All-Out Running Efforts","volume":"12","author":"McFarlin","year":"2021","journal-title":"Front. Physiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1097\/CJI.0b013e3182518e83","article-title":"Cancer and innate immune system interactions: Translational potentials for cancer immunotherapy","volume":"35","author":"Liu","year":"2012","journal-title":"J. Immunother."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Chernosky, N.M., and Tamagno, I. (2021). The Role of the Innate Immune System in Cancer Dormancy and Relapse. Cancers, 13.","DOI":"10.3390\/cancers13225621"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1046\/j.1525-1438.2000.00003.x","article-title":"Cytokines IL-1beta, IL-2, IL-6, IL-8, MCP-1, GM-CSF and TNFalpha in patients with epithelial ovarian cancer and their relationship to treatment with paclitaxel","volume":"10","author":"Penson","year":"2000","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1093\/bjaceaccp\/mkh040","article-title":"Endocrine and metabolic response to surgery","volume":"4","author":"Burton","year":"2004","journal-title":"Contin. Educ. Anaesth. Crit. Care Pain"}],"container-title":["Metabolites"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-1989\/13\/3\/417\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:53:05Z","timestamp":1760122385000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-1989\/13\/3\/417"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,12]]},"references-count":53,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["metabo13030417"],"URL":"https:\/\/doi.org\/10.3390\/metabo13030417","relation":{},"ISSN":["2218-1989"],"issn-type":[{"value":"2218-1989","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,12]]}}}